THE METABOLISM OF DRUGS BY LIVER MICROSOMES FROM ALLOXAN-DIABETIC RATS: LONG TERM DIABETES

¹ Department of Pharmacology, College of Medicine, State University of Iowa, Iowa City, Iowa

Diabetes induced by alloxan affected several microsomal drug metabolic pathways measured over a 3-month period. A depressed metabolism of hexobarbital and aminopyrine in vitro, an increased in vitro hydroxylation of aniline, and a prolonged in vivo effect of hexobarbital were evident. The O-dealkylation of codeine was unaffected by the chronic diabetic state. Insulin treatment returned the rate of metabolism of hexobarbital to normal levels but had no effect on aminopyrine metabolism. Metabolism of aniline was decreased below the normal rate after insulin treatment.

Phenobarbital treatment of diabetic animals resulted in a stimulation of most of the drug metabolizing enzyme systems studied. However, the hydroxylation of aniline by livers from diabetic rats treated with phenobarbital was decreased.

A possible relationship between hepatic levels of glycogen and drug-metabolizing enzyme activity has been suggested. The results reported are compatible with the hypothesis that alterations of hepatic ultrastructure result in an alteration of function.

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